Phencyclidine (PCP) and sigma receptors, though linked in terms of their historical development, and their generally high affinity interactions with (+)-opiates, are now known to be pharmacologically and biochemically distinct binding sites. The PCP binding site, because it is but one component of the NMDA receptor, is relevant to drug abuse research because the NMDA receptor plays important roles in neuronal processes involved in substance abuse, such as memory, propagation of seizures and kindling. Previous studies showed that the PCP analog, (3H)TCP labels two high affinity PCP binding sites: PCP site 1 (NMDA-receptor-associated) and PCP site 2 (biogenic-amine -transporter-associated). Recent results showed that lesioning caudates with MPTP partially decreased PCP site 2, consistent with it being localized in part on the DA nerve terminals. Other structure-activity studies demonstrated that certain reuptake inhibitors and potassium channel blockers show a high degree of selectivity for PCP site 2. Other experiments showed that in crude membrane preparations, glutamate modulated [3H)TCP binding via an allosteric mechanism, not a steric hinderance mechanism, as is the case in well-washed membranes. Although the function of sigma receptors awaits final clarification, some data indicate a role for sigma receptors as modulators of cocaine-induced locomotor activity and in various dystonias. Recent findings from the CPS include the identification of two drugs out of 89 newly synthesized compounds, which permitted resolution of two sl binding sites, and the partial characterization of a trace contaminant in HEPPSO buffer which has high affinity for the sigma binding site.